AB1098 DEUCRAVACITINIB IN PLAQUE PSORIASIS: 2-YEAR LABORATORY RESULTS FROM THE PHASE 3 POETYK PSO PROGRAM
Authors: N. J. Korman, T. Passeron, K. B. Gordon, Y. Okubo, J. Bagel, H. Sofen, R. B. Warren, N. Bhatia, L. Spelman, K. Winthrop, L. Hippeli, R. M. Kisa, S. Banerjee, D. Thaçi
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Tyrosine kinase 2 (TYK2) is an intracellular enzyme involved in IL-23 signaling that is important in the pathogenesis of immune-mediated diseases, including psoriasis, psoriatic arthritis, and systemic lupus erythematosus (SLE). Deucravacitinib is a first-in-class, oral, selective, allosteric TYK2 inhibitor approved in multiple countries for the treatment of adults with plaque psoriasis. Deucravacitinib uniquely binds to the TYK2 regulatory domain rather than the more conserved catalytic domain at which Janus kinase (JAK) 1/2/3 inhibitors bind. Deucravacitinib was efficacious compared with placebo in phase 2 trials in psoriatic arthritis and SLE.<sup>[1,2]</sup> Furthermore, deucravacitinib was significantly more efficacious than placebo or apremilast and was well tolerated in patients with moderate to severe plaque psoriasis, as observed in the phase 3 POETYK PSO-1 and PSO-2 trials.<sup>[3,4]</sup> Patients who completed the psoriasis trials could enroll in the ongoing open-label, 240-week long-term extension (LTE) trial. <h3>Objectives</h3> This analysis examined whether changes occurred in blood laboratory parameters upon deucravacitinib treatment in the phase 3 POETYK PSO-1, PSO-2, and LTE trials and, if so, assessed how these compared with signature laboratory changes seen with JAK 1/2/3 inhibitors. <h3>Methods</h3> POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) were 52-week, double-blind trials that randomized patients with moderate to severe plaque psoriasis 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily. Patients receiving placebo switched to deucravacitinib at Week 16, and patients receiving apremilast who failed to achieve ≥50% reduction from baseline in Psoriasis Area and Severity Index (PASI 50; PSO-1) or ≥75% reduction from baseline in PASI (PASI 75; PSO-2) at Week 24 switched to deucravacitinib. At Week 52, all eligible patients enrolled in the LTE trial (NCT04036435) and received open-label deucravacitinib 6 mg once daily. Changes from baseline in hematologic parameters (lymphocytes, neutrophils, platelets, hemoglobin) and lipid and chemistry parameters (cholesterol, creatinine, CPK, ALT) known to be impacted by JAK 1/2/3 inhibitors were assessed through Week 100 (LTE at Week 48). CTCAE grade ≥3 laboratory abnormalities and treatment discontinuations due to laboratory abnormalities were also evaluated. <h3>Results</h3> Patients (n=1519) received ≥1 dose of deucravacitinib in PSO-1, PSO-2, and/or the LTE through the cutoff date of 1 October 2021. In total, 1179 (77.6%) and 584 (38.4%) patients had ≥52 and ≥104 weeks, respectively, of continuous deucravacitinib exposure at the cutoff date, and the median duration of exposure was 682.0 days (97 weeks). No trends for clinically meaningful changes from baseline were observed in any laboratory parameters from Weeks 0–52 in PSO-1 or in the LTE. Grade 3 or 4 abnormalities over 100 weeks of deucravacitinib treatment were rare; incidence rates were comparable with placebo and apremilast through Week 52, and no increases were seen in the LTE. Two patients discontinued deucravacitinib treatment due to laboratory abnormalities (1 lymphopenia, 1 abnormal hepatic function). <h3>Conclusion</h3> No trends for clinically meaningful changes from baseline were observed with deucravacitinib treatment in hematologic, lipid, or chemistry parameters, including signature laboratory changes associated with JAK 1/2/3 inhibitors, for up to 100 weeks. Treatment discontinuations and grade 3 or 4 laboratory abnormalities were rare, consistent with those in the parent studies, and comparable to the incidence rates seen with placebo and apremilast. These results suggest that laboratory monitoring in patients with plaque psoriasis is not warranted with deucravacitinib treatment. <h3>References</h3> [5]Mease PJ, et al. <i>Ann Rheum Dis</i>. 2022;81:815-822. [6] Morand E, et al. <i>Arthritis Rheumatol</i>. 2022 Nov 11. doi: 10.1002/art.42391. Epub ahead of print. [7] Armstrong AW, et al. <i>J Am Acad Dermatol.</i> 2023;88:29-39. [8] Strober B, et al. <i>J Am Acad Dermatol.</i> 2023;88:40-51. <h3>Acknowledgements</h3> These clinical trials were sponsored by Bristol Myers Squibb. <h3>Disclosure of Interests</h3> Neil J Korman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Regeneron, and Sanofi Genzyme, Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Principia, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Argenx, Bristol Myers Squibb, Celgene, Chemocentryx, Eli Lilly, Galderma, Kyowa Hakko Kirin, Leo Pharma, Menlo, Principia, Prothena, Rhizen, Syntimmune, Trevi, and XBiotech, Thierry Passeron Consultant of: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Incyte, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi Genzyme, Sun Pharma, and UCB, Kenneth B Gordon Consultant of: Almirall, Amgen, Dermira, Leo Pharma, Pfizer, and Sun Pharma, Grant/research support from: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, and UCB, Yukari Okubo Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eisai, Eli Lilly, Janssen Pharma, Jimro, Kyowa Kirin, Leo Pharma, Maruho, Novartis, Pfizer, Sanofi, Sun Pharma, Taiho, Tanabe-Mitsubishi, Torii, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, and Sun Pharma, Grant/research support from: Eisai, Maruho, Shiseido, and Torii. AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Maruho, Pfizer, Sun Pharma, and UCB, Jerry Bagel Speakers bureau: AbbVie, Celgene, Eli Lilly, Janssen Biotech, and Novartis, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Janssen Biotech, Novartis, Sun Pharma, and Valeant, Grant/research support from: AbbVie, Amgen, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, CorEvitas' (Corrona) Psoriasis Registry, Dermavant, Dermira/UCB, Eli Lilly, Glenmark, Janssen Biotech, Kadmon, Leo Pharma, Lycera, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sun Pharma, Taro, and Valeant, Howard Sofen Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis, and Sun Pharma, Richard B. Warren Consultant of: AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, DiCE Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and UNION, Grant/research support from: AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, and UCB, Neal Bhatia Consultant of: AbbVie, Almirall, Arcutis, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, InCyte, ISDIN, Johnson &amp; Johnson, Leo Pharma, Lilly, Ortho, Pfizer, Regeneron, Sanofi, Stemline, and Sun Pharma, Grant/research support from: Arcutis, Biofrontera, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Galderma, Leo Pharma, Lilly, and Ortho, Lynda Spelman Consultant of: AbbVie, Amgen, Anacor, Ascend, Astellas, AstraZeneca, Blaze Bioscience, Bristol Myers Squibb, Boehringer Ingelheim, Botanix, Celgene, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Hexima, Janssen, Leo Pharma, Mayne, Medimmune, Merck, Merck-Serono, Novartis, Otsuka, Pfizer, Phosphagenics, Photon MD, Regeneron, Roche, Samumed, Sanofi Genzyme, SHR, Sun Pharma ANZ, Trius, UCB, and Zai Lab, Kevin Winthrop Consultant of: AbbVie, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Novartis, Pfizer, Regeneron, Roche, Sanofi, and Union Chimique Belge (UCB), Grant/research support from: Bristol Myers Squibb and Pfizer, Lauren Hippeli Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Renata M Kisa Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Subhashis Banerjee Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Diamant Thaçi Speakers bureau: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi, Target-Solution, and UCB, Consultant of: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi, Target-Solution, and UCB, Grant/research support from: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi, Target-Solution, and UCB.